Antibiotic Treatment for Empyema Necessitans Caused by CRAB and CRPA

Treatment Strategy for Dual CRAB/CRPA Infection

• The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) recommends using combination therapy with polymyxin B (or colistin) plus a second in vitro active agent for empyema necessitans caused by both CRAB and CRPA, guided by antimicrobial susceptibility testing, along with aggressive surgical drainage 1, 2, 3
• For the CRAB component, the Infectious Diseases Society of America (IDSA) suggests first-line treatment with ampicillin-sulbactam if sulbactam-susceptible, and polymyxin B or high-dose tigecycline if sulbactam-resistant 1, 4
• The IDSA recommends against using cefiderocol for CRAB treatment, and avoiding polymyxin-meropenem or polymyxin-rifampin combinations for CRAB 1, 4

Antibiotic Selection Framework

• For the CRPA component, the ESCMID suggests using ceftolozane-tazobactam as the first choice for severe difficult-to-treat CRPA if susceptible 1, 2
• If ceftolozane-tazobactam is unavailable or resistant, consider imipenem-relebactam, cefiderocol, or ceftazidime-avibactam based on susceptibility 1, 2
• For polymyxin-based therapy, combine polymyxin with a second in vitro active agent (aminoglycoside, fosfomycin, or carbapenem if MIC ≤8 mg/L) 1, 4, 2, 3

Recommended Combination Approach

• Given dual infection, the practical regimen should cover both organisms, such as ampicillin-sulbactam PLUS ceftolozane-tazobactam if CRAB is sulbactam-susceptible and CRPA is ceftolozane-tazobactam-susceptible 1, 2
• If both organisms are resistant to preferred agents, use polymyxin B (with loading dose for critically ill patients) PLUS two additional agents active against at least one organism each (e.g., aminoglycoside + high-dose tigecycline or fosfomycin) 1, 2, 3

Critical Management Principles

• Use therapeutic drug monitoring when available, particularly for polymyxins and aminoglycosides 2, 3
• Employ high-dose extended-infusion dosing for carbapenems if used (when MIC ≤8 mg/L) 3

Common Pitfalls to Avoid

• Never use polymyxin monotherapy for severe CRPA infections, as it is associated with higher treatment failure 2
• Avoid carbapenem-polymyxin combinations for CRPA unless meropenem MIC is ≤8 mg/L with high-dose extended infusion 1, 4

Nuances in Evidence

• The ESCMID guidelines acknowledge very low certainty of evidence for combination therapy recommendations in CRPA, but suggest it over monotherapy for severe infections 1, 4, 2